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CHMP2B mutations are rare in French families with frontotemporal lobar degeneration

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Abstract

Two C-truncating CHMP2B (chromatin modifying protein 2B) mutations were recently found in Danish and Belgian families with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). In addition, few CHMP2B missense mutations of uncertain pathogenic role were reported in several families with FTLD or FTLD associated with motoneuron disease (FTLD-MND). In order to determine the genetic contribution of CHMP2B mutations in FTLD and FTLD-MND families, we analyzed the CHMP2B gene in 198 French probands with familial FTLD and FTLD-MND. One CHMP2B missense variant was found in a proband with familial FTLD (0.8%). The pathogenic role of CHMP2B missense variants is unclear, however the pSer194Leu substitution, located in the C-terminal domain of the protein, was predicted to alter the stability of the protein by in silico analyses. We conclude that CHMP2B mutations represent a rare cause of familial FTLD and they are not implicated in familial FTLD-MND in French patients. The previously reported C-truncating CHMP2B mutations may be private to the Danish and Belgian pedigrees.

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Acknowledgments

We thank Ms. Lydia Guennec, Isabelle Lagroua, and Christelle Dussert (DNA and cell bank of CR-ICM UMRS_975, Hôpital de la Salpêtrière, Paris) for their excellent technical assistance and the Dr. Sophie Rivaud-Pechoux for statistical analyses (CR-ICM UMRS_975, Hôpital de la Salpêtrière, Paris). This study was supported by ANR R6363DS (to A.B.), France Alzheimer association (to A.B), ANR R08104DS (to ILB), and ARsla (to A.B.).

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. CRicm INSERM UMRS_975, 75013, Paris, France

    Mustapha Ghanim, Léna Guillot-Noel, Ludmila Jornea, Bruno Dubois, Isabelle Le Ber & Alexis Brice

  2. Department of Neurology and EA2691, University Hospital, Lille, France

    Florence Pasquier & Vincent Deramecourt

  3. Centre de Référence des démences rares, Hôpital de la Pitié-Salpêtrière, Paris, France

    Bruno Dubois, Isabelle Le Ber & Alexis Brice

  4. Département des maladies du système nerveux, AP-HP, Hôpital de la Pitié-Salpêtrière, 75013, Paris, France

    Bruno Dubois, Isabelle Le Ber & Alexis Brice

  5. UPMC Paris06, UMR_S679, 75005, Paris, France

    Bruno Dubois & Alexis Brice

  6. Département de Génétique et Cytogénétique, AP-HP, Hôpital de la Pitié-Salpêtrière, 75013, Paris, France

    Alexis Brice

  7. CR-ICM UMR_S 975, Hôpital de la Salpêtrière, 47 Boulevard de l’hôpital, 75 651, Paris Cedex 13, France

    Alexis Brice

Authors
  1. Mustapha Ghanim
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  2. Léna Guillot-Noel
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  3. Florence Pasquier
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  4. Ludmila Jornea
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  5. Vincent Deramecourt
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  6. Bruno Dubois
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  7. Isabelle Le Ber
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  8. Alexis Brice
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Consortia

The French Research Network on FTD and FTD/MND

Corresponding author

Correspondence to Alexis Brice.

Additional information

The members of the French research network on FTD and FTD/MND are given in the Appendix.

M. Ghanim and L. Guillot-Noel equally contributed to this work.

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Appendix

Appendix

The French clinical and genetic research network on FTD/FTD-MND includes: Alexis Brice (Hôpital de la Salpêtrière, Paris), Frédéric Blanc (Hôpitaux Civils, Strasbourg), William Camu (CHU Gui de Chauliac, Montpellier), Françoise Clerget-Darpoux (Hôpital Paul Brousse, Villejuif), Philippe Corcia (CHU Tours), Mira Didic (CHU La Timone, Marseille), Bruno Dubois (Hôpital de la Salpêtrière, Paris), Charles Duyckaerts (Hôpital de la Salpêtrière, Paris), Marie-Odile Habert (Hôpital de la Salpêtrière, Paris), Véronique Golfier (CHU Rennes), Eric Guedj (CHU Marseille), Didier Hannequin (CHU Charles Nicolle, Rouen), Lucette Lacomblez (Hôpital de la Salpêtrière, Paris), Isabelle Le Ber (Hôpital de la Salpêtrière, Paris), Richard Levy (CHU St Antoine, Paris), Vincent Meininger (Hôpital de la Salpêtrière, Paris), Bernard-François Michel (CH Sainte-Marguerite, Marseille), Florence Pasquier (CHU Roger Salengro, Lille), Catherine Thomas-Anterion (CHU Bellevue, Saint-Etienne), Michèle Puel (CHU Rangueil, Toulouse), François Salachas (Hôpital de la Salpêtrière, Paris), François Sellal (CH Colmar), Martine Vercelletto (CHU Laennec, Nantes), Patrice Verpillat (Hôpital de la Salpêtrière, Paris).

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Ghanim, M., Guillot-Noel, L., Pasquier, F. et al. CHMP2B mutations are rare in French families with frontotemporal lobar degeneration. J Neurol 257, 2032–2036 (2010). https://doi.org/10.1007/s00415-010-5655-8

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  • DOI: https://doi.org/10.1007/s00415-010-5655-8

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